It is proposed to conduct a detailed analysis of the degree of quantitative correspondence between synaptic vesicle patterns, other E.M. variables, and EPSP amplitude during repetitive stimulation in the hippocampus of aging and young rats. Except for one preliminary study we conducted earlier, there have apparently been no studies on the relations of vesicles to synaptic physiology during stimulation of a well-defined synaptic system in the mammalian brain. No systematic study of vesicle patterns has previously been conducted in relation to aging. Most studies comparing vesicles and physiology have utilized stimulation that depresses synaptic EPSPs. It is therefore proposed to study these phenomena in a brain system in which, with appropriate parameters, very robust frequency potentiation occurs (Schaffer collateral-commissurals). The examination of vesicle patterns and other E.M. parameters under conditions of both synaptic potentiation and depression, seems likely to contribute new perspectives to the issue of how closely vesicle patterns correspond to transmitter release patterns, and may clarify the presynaptic mechanisms of hippocampal frequency potentiation. Since we have previously defined a consistent deficit in hippocampal frequency potentiation in aging rats, these studies seem likely to yield valuable insights into basic principles of synaptic decline during mammalian aging.